Mechanisms Associated with Hypersensitivity

TABLE 32.7. Gell and Coombs Classification of Hypersensitivity Reactions 

Type I Cytophilic antibody (IgE) binds to mast cells antigen binds to antibody and crosslinks receptors, causing mediator (histamine) release immediate hypersensitivity 

Type III IgM, IgG complexed with antigen (immune complexes) leading to inflammation Type IV T-cell-mediated delayed-type hypersensitivity 

1 Classification of Immune-Mediated Injury Based on Mechanisms 

Type III reactions are the result of antigen-antibody (IgG) complexes that accumulate in tissues or the circulation, activate macrophages and the complement system, and trigger the influx of neutrophils, eosinophils, and lymphocytes (inflam- 

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Cremophor EL may be implicated in the incidence of dysrhythmias, particularly as a result of hypotension associated with hypersensitivity reactions [34 ]. Another mechanism may be through histamine release, which in animab results in conduction disturbances and dysrhythmias [35 ]. 

Two current foci in pain management are to identify the mechanisms that are responsible for pain hypersensitivity and to prevent this initial hypersensitivity. Therefore, the goal of pain therapy is to reduce peripheral sensitization and subsequent central stimulation and amplification associated with wind-up, spread, and central sensitization.17... 

Clinical pain is characterized by the presence of spontaneous pain or hypersensitivity to pain-provoking stimuli. Hypersensitivity includes pain produced by low-intensity stimuli that normally only elicit an innocuous sensation (allodynia), or an exaggerated response to a noxious stimulus (hyperalgesia). There are two distinct forms of clinical pain, the pain that occurs after tissue injury or inflammatory diseases (inflammatory pain) and the pain associated with a lesion or disease of the nervous system (neuropathic pain). Although the mechanisms responsible for the initiation and maintenance of these pains differ, they are both characterized by heightened... 

Hypersensitivity or idiosyncrasy to quinidine or other cinchona derivatives manifested by thrombocytopenia, skin eruption or febrile reactions myasthenia gravis history of thrombocytopenic purpura associated with quinidine administration digitalis intoxication manifested by arrhythmias or AV conduction disorders complete heart block left bundle branch block or other severe intraventricular conduction defects exhibiting marked QRS widening or bizarre complexes complete AV block with an AV nodal or idioventricular pacemaker aberrant ectopic impulses and abnormal rhythms due to escape mechanisms history of drug-induced torsade de pointes history of long QT syndrome. 

Cardiovascular effects. Hypotension and tachycardia occur in most patients taking clozapine. Cases of potentially fatal myocarditis and dilated cardiomyopathy have been reported in association with clozapine (Kilian et al. 1999). Myocarditis typically occurred within 3 weeks of starting clozapine, but cardiomyopathy may not be apparent for several years. Although rare, treatment-emergent myocarditis and cardiomyopathy occur at a reportedly higher incidence with clozapine than with other antipsychotics (Coulter et al. 2001). The mechanism by which clozapine may cause myocarditis has not been established, but some authors have speculated that clozapine may cause an immunoglobuhn E (IgE)-mediated type 1 hypersensitivity reaction (Kihan et al. 1999) or a hypereosinophilic syndrome (Hagg et al. 2001). 

The adverse effects of ALG are mostly those associated with injection of a foreign protein. Local pain and erythema often occur at the injection site (type III hypersensitivity). Since the humoral antibody mechanism remains active, skin-reactive and precipitating antibodies may be formed against the foreign IgG. Similar reactions occur with monoclonal antibodies of murine origin, and reactions thought to be caused by the release of cytokines by T cells and monocytes have also been described. 

Drug reactions mediated by immune responses can have several different mechanisms. Thus, any of the four major types of hypersensitivity discussed earlier in this chapter (page 967) can be associated with allergic drug reactions ... 

Levamisole was first synthesized for the treatment of parasitic infections. Later studies suggested that it increases the magnitude of delayed hypersensitivity or T cell-mediated immunity in humans. In immunodeficiency associated with Hodgkin s disease, levamisole has been noted to increase the number of T cells in vitro and to enhance skin test reactivity. Levamisole has also been widely tested in rheumatoid arthritis and found to have some efficacy. However, it has induced severe agranulocytosis (mainly in HLA-B27-positive patients), which required discontinuation of its use. The drug may also potentiate the action of fluorouracil (5-FU) in adjuvant therapy of colorectal cancer, and this combination has been approved for clinical use in the treatment of Dukes class C colorectal cancer after surgery. Its use in these cases reduces recurrences, and the mechanism... 

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